Archaic chaperone-usher pili self-secrete into superelastic zigzag springs

Area of Science:

• Microbiology
• Structural Biology
• Biophysics

Background:

• Adhesive pili are crucial for Gram-negative bacterial colonization and biofilm formation.
• Archaic chaperone-usher pathway pili are prevalent in multidrug-resistant pathogens, making them key targets for vaccines and drugs.
• The structure and assembly mechanism of archaic pili were previously unknown.

Purpose of the Study:

• To determine the cryo-electron microscopy structure of the prototypical archaic Csu pilus from Acinetobacter baumannii.
• To elucidate the assembly and secretion process of archaic pili.
• To explore the mechanical properties and potential therapeutic implications of the archaic pilus structure.

Main Methods:

• Cryo-electron microscopy (cryo-EM) to determine the 3D structure of the Csu pilus.
• Biophysical analysis to assess the mechanical stability and elasticity of the pilus.
• Cell-based assays to investigate the role of clinch formation in pilus secretion.

Main Results:

• The archaic Csu pilus adopts an ultrathin zigzag architecture, distinct from classical pili.
• A novel molecular clinch mechanism provides high mechanical stability and superelasticity to the pilus.
• Clinch formation was identified as the driving force for pilus secretion through the outer membrane.
• This assembly process is more economical and faster than previously understood mechanisms.

Conclusions:

• The unique zigzag architecture and clinch mechanism of archaic pili contribute to their stability and assembly efficiency.
• The findings reveal a novel mechanism for pilus secretion in Gram-negative bacteria.
• Inhibitors targeting clinch formation could offer a new therapeutic strategy against multidrug-resistant bacterial infections.